Journal of immunology research · 2019
KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico.
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Machado-Sulbaran Andrea Carolina, Ramírez-Dueñas María Guadalupe, Navarro-Zarza José Eduardo, Muñoz-Valle José Francisco, Mendoza-Carrera Francisco, Baños-Hernández Christian Johana, Parra-Rojas Isela, Montoya-Buelna Margarita, Sánchez-Hernández Pedro Ernesto
Аннотация
INTRODUCTION: Systemic Sclerosis (SSc) is an autoimmune, inflammatory, and multisystemic disease characterized by the presence of autoantibodies and fibrosis. The pathogenesis involves the interaction between immune system cells such as macrophages, NK cells, T cells, and B cells. Killer-cell Immunoglobulin-like Receptors (KIR) are expressed in NK cells and some T cell subsets that recognize HLA class I molecules as ligands and are involved in regulating the activation and inhibition of these cells. The KIR family consists of 14 genes and two pseudogenes; according to the gene content, the genotype could be AA and Bx. The aim of this study was to evaluate the association between KIR/HLA genes and genotypes with SSc and the clinical characteristics.
METHODS: We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A ∗ 03/ ∗ 11 was made by SSP-PCR.
RESULTS: In SSc patients, a higher frequency of KIR2DL2 (p = 0.0007, p' = 0.011), KIR2DS4del (p = 0.001, p' = 0.021), and HLA-C2 (p = 0.02, p' = 0.09) was found. This is the first study to evaluate the frequency of HLA-A ∗ 03/ ∗ 11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p = 0.007, OR = 3.1, 95% CI = 1.4-7.9, p' = 0.014). The genotypes with a higher iKIR number than aKIR (iKIR > aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics.
CONCLUSION: The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.
METHODS: We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A ∗ 03/ ∗ 11 was made by SSP-PCR.
RESULTS: In SSc patients, a higher frequency of KIR2DL2 (p = 0.0007, p' = 0.011), KIR2DS4del (p = 0.001, p' = 0.021), and HLA-C2 (p = 0.02, p' = 0.09) was found. This is the first study to evaluate the frequency of HLA-A ∗ 03/ ∗ 11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p = 0.007, OR = 3.1, 95% CI = 1.4-7.9, p' = 0.014). The genotypes with a higher iKIR number than aKIR (iKIR > aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics.
CONCLUSION: The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.